Histamine is a member of autacoids acting in the living body, abundant in the skin, lung, digestive organs, and so on, which is released in allergy and anaphylaxis and associated with the onset of urticaria or inflammation or hematopoiesis. In the gastric mucosa, it has been found that histamine is involved in the generation of gastric ulcers because it is present in the enterochromaffin cells to play an important role in promoting secretion of gastric juice.
Thus, since histamine is involved in a variety of human disorders and alteration of physical condition, elucidation of the mechanism of its action is essential for development of the therapeutics and remedies used in histamine-related diseases. Since these diseases or change of physical condition arise in the context of i various tissues or organs in the body, it is indispensable to study the effect of histamine in vivo using a model animal.
In this viewpoint, the inventors of the present application have already invented knockout animals (animals lackng in histamine) in which th gene for histamine synthetase has been knocked out, and filed as the Japanese Patent Application no. 11-246315 (1999). However, animals expressing histamine in excess have not yet been known.
Therefore, it has eagerly been desired to develop a model animal system by which a variety of symptoms in animal individuals in the excess state of histamine could be analyzed systematically. It has also been expected that such model animals might be a powerful tool for developing remedies used in treatment of a variety of disorders associated with histamine.
The invention was made in view of the above-mentioned situation, aiming for providing animals with high histamine productivity, capable of producing histamine in excess in the body.